Atherosclerotic Lesions Rich in
Macrophages or Smooth Muscle
Cells Discriminated in Rabbit Iliac
Arteries Based on T1 Relaxation Timeand Lipid Content
Yasuyoshi Kuroiwa, MS, Atsushi Yamashita, MD, PhD, Tosiaki Miyati, PhD, DMSc, Eiji Furukoji, MD,
PhD, Misaki Takahashi, MS, Toshiya Azuma, PhD, Hiroshi Sugimura, MD, PhD, Shozo Tamura, MD,
PhD, Keiichi Kawai, PhD, Yujiro Asada, MD, PhD
Rationale and Objectives: Atherothrombosis usually occurs on macrophage- and lipid-rich unstable plaque, but rarely on smooth muscle
cell (SMC)-rich stable plaque. Magnetic resonance imaging (MRI) has been extensively applied for noninvasive vascular imaging. We therefore investigated whether MRI provides valuable information about the characteristics of atherosclerotic vessels using rabbit models ofmacrophage-rich or SMC-rich atherosclerotic arteries.
Materials and Methods: Rabbits were fed with a conventional (CD group, n = 3) or 0.5% cholesterol (ChD group, n = 3) diet for 1 week
before and 3 weeks after balloon injury of the left iliac arteries. Three weeks later, these arteries were investigates by 1.5 T MRI and by
conventional angiographic imaging, followed by histological and immunohistochemical analyses.
Results: Three weeks after balloon injury, injured iliac arteries of both groups formed neointima with luminal stenosis. Conventional and
MRI angiographic findings of the luminal diameter significantly and positively correlated. T1 relaxation time was significantly shorter and thelipid content was much higher in injured arteries from the ChD than from the CD group. The injured arteries from the ChD also contained
more macrophages and less SMCs that those from the CD group. The T1 relaxation time and lipid content in injured arteries negatively andpositively correlated with the degree of macrophage accumulation, respectively.
Conclusion: These results showed that MRI could provide valuable information about luminal stenosis and the characteristics of atherosclerotic vessels in rabbits.
Key Words: Magnetic resonance imaging; atherosclerosis; macrophage; smooth muscle cell.
ªAUR, 2010T

hrombus formation after atherosclerotic plaquedisruption is a major cause of acute coronary syndrome
and stroke. Atherothrombosis usually occurs on
macrophage- and lipid-rich unstable plaque, but rarely onsmooth muscle cell (SMC)-rich stable plaque (1). Besideluminal stenosis, plaque composition and morphology are

Acad Radiol 2010; 17:230–238
From the Department of Radiological Technology, Koga General Hospital,
Miyazaki (Y.K.); Departments of Pathology (Y.K., A.Y., M.T., Y.A.) and ofRadiology (E.F., T.A., H.S., S.T.), Faculty of Medicine, University of Miyazaki,
5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan; Division of Health
Sciences, Graduate School of Medical Science, Kanazawa University,
Ishikaw (Y.K., T.M., T.A., K.K.); and Biomedical Imaging Research Center,
University of Fukui, Fukui, Japan (K.K.). Received June 24, 2009; accepted
September 8, 2009. Address correspondence to: Y.A. e-mail: yasada@fc.
miyazaki-u.ac.jpªAUR, 2010
doi:10.1016/j.acra.2009.09.008

230

key determinants of whether a plaque will cause cardiovascular events. Despite major advances in treatment, a high ratioof apparently healthy and asymptomatic patients dies ofatherosclerosis (2). Therefore the development of screening
and diagnostic methods to identify and characterize plaquecomposition is very important to determine the patientspecific risk of cardiovascular events and improve treatment
strategies.
Magnetic resonance imaging (MRI) is used extensively fornoninvasive vascular imaging, because it can identify components of atherosclerotic plaques such as a lipid-rich/necrotic
core, calcification, and hemorrhage (3,4). It can also visualize
and quantify lipid-rich human carotid plaque (5–7) and the
rabbit aorta (8). However, whether or not MRI can distinguish between stable and unstable atherosclerotic vessels invivo is unknown. The aim of the study is to investigate
whether MRI can distinguish between rabbit iliac arteries
with macrophage-rich and SMC-rich atherosclerotic lesions.

Academic Radiology, Vol 17, No 2, February 2010

DISCRIMINATION OF UNSTABLE AND STABLE PLAGUE

Figure 1. Representative magnetic resonance (MR) angiograms of rabbit iliac arteries.
MR angiograms of the conventional cholesterol group (CD) (a) and 0.5% cholesterolgroup (ChD) (b) rabbits. Injured iliac arteries(left) of both groups have a narrower lumen(arrows) than uninjured arteries. (c) Luminal
diameters of uninjured arteries (open box)
and 3 weeks (dotted box) after balloon injury.
(n = 6 each; *P < .001). Data are presented
as medians (horizontal bar), quartile ranges(boxes), and 90th percentiles (error bars). (d)Linear regression analysis of associations
between conventional and MR angiography
with respect to luminal diameter.

MATERIALS AND METHODS
Experimental Design

Six male Japanese white rabbits weighing 2.5–3.0 kg were fed
with a conventional diet (CD group; n = 3) or a 0.5% cholesterol diet (ChD group; n = 3) for 1 week before and 3 weeks
after balloon injury. All surgical manipulations proceeded
under aseptic conditions and general anesthesia elicited byan intravenous injection of pentobarbital (25 mg/kg, bodyweight). One week after starting the diets, an angioplasty
balloon catheter (2.75-mm diameter, 18-mm length; Potenza,
Japan Lifeline Co, Osaka, Japan) was inserted via the carotid
artery into the left iliac arteries under fluoroscopic guidance.
The catheter was inflated to 1.5 atm (balloon-to-artery ratio;
1.1:1 to 1.2:1) and retracted by 5 cm three times to denude theendothelium (9). Three weeks after balloon injury, the iliac
arteries were visualized by MRI and conventional angiography, and the images were analyzed at 4-mm intervals.
Immediately after conventional angiography, the rabbits
were injected with heparin (500 U/kg, IV) and then killedwith an overdose of pentobarbital (60 mg/kg, IV) 5 minutes
later. The animals were perfused with 50 mL of 0.01 mol/L
phosphate buffered saline and then perfusion-fixed with 4%paraformaldehyde for histological and immunohistochemicalevaluation.
The Animal Care Committees of our institutions
approved our animal research protocols. This investigation
also conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of
Health.
231

KUROIWA ET AL

Academic Radiology, Vol 17, No 2, February 2010

Figure 2. In vivo axial magnetic resonance (MR) images and MR parameters of rabbit iliac arteries. (a) Luminal narrowing appears as thicker
walls in injured arteries (arrows) of both groups compared with uninjured arteries. Thickened artery of 0.5% cholesterol (ChD) rabbit shows lowor high-signal intensity in T1-weighted image with or without fat saturation, respectively. (b) T1 and T2 relaxation times and lipid contents of iliac
arteries in the conventional cholesterol (CD) and ChD groups, uninjured arteries (open box) and 3 weeks after balloon injury (dotted box) (n = 6
each; *P < .001). Data are shown as medians (horizontal bar), quartile ranges (boxes), and 90th percentiles (error bars).

232

Academic Radiology, Vol 17, No 2, February 2010

DISCRIMINATION OF UNSTABLE AND STABLE PLAGUE

Figure 3. Representative microphotographs
and linear regression analyses of iliac arteries 3
weeks after balloon injury. (a) Microphotographsof injured iliac arteries in both groups. Neointima
has formed in injured iliac arteries. N: neointima;
M: media; Ad: adventitia. (b) Immunopositive
areas for RAM11 and HHF35 of iliac arteries 3
weeks after balloon injury in both groups (n = 6
each; *P < .05). Data are presented as medians(horizontal bar), quartile ranges (boxes), and90th percentiles (error bars). (c) Linear regression
analysis of associations between relaxation
times and immunopositive areas in injured iliac
arteries.

MRI

Three weeks after the first injury, rabbits were anesthetizedand placed in the supine position in a 1.5-T superconductive
magnet unit (Excelart Vantage XGV Power Plus Package,
Toshiba Medical Systems, Tokyo, Japan) using a quadratureknee radiofrequency coil, then MRI proceeded with the
rabbits in the left decubitus position. The abdominal aorta
and femoral artery were localized using gradient-echo coronal
images. Thereafter, transverse sequential images of the iliac
artery from the abdominal aorta to the femoral artery wereacquired using three-dimensional (3D) time-of-flight andthe following parameters: repetition time/echo time (TR/TE), 40/6.8 ms; flip angle (FA), 20 and one excitation.
The MRI angiography images were reconstructed in 3D
using maximum intensity projection as a post-processing
tool. The luminal diameter was measured on maximum intensity projection images for comparison with conventional
angiography. 3D-gradient echo T1-weighted images(T1WI) were obtained using the following parameters: TR/
TE, 38/5.0 ms; FA 20 and 40 , and two excitations without

fat suppression pulses. Images of the ratio (%) of fat content
were generated using fat suppression 3D-gradient echo
T1WI at TR/TE, 38/5.0 ms and FA 20 . We acquired 3D
fast advanced spin echo proton density-weighted and T2weighted images at TR/TE, 2000/34 and 2000/80 ms,
respectively. The pixels on the images were 0.46  0.46
mm in area, slice thickness was 1 mm, and the number of excitations was two.
Ex vivo Study

Four male Japanese white rabbits were fed with a conventional
diet (n = 2) or a 0.5% cholesterol diet (n = 2) for 1 week
before and 3 weeks after balloon injury of the bilateral iliac
arteries. The rabbits were injected with heparin (500 U/kg,
IV) 3 weeks after the balloon injury, and killed with an overdose of pentobarbital (60 mg/kg, IV) 5 minutes later. The
animals were perfused with 50 mL of 0.01 mol/L phosphatebuffered saline, and then the excised iliac arteries were examined by MRI at 37 C using the same parameters as the study
in vivo.
233

KUROIWA ET AL

Academic Radiology, Vol 17, No 2, February 2010

Figure 3. (continued).

Image and Data Analysis

The MRIs were transferred to a Macintosh computer for
further analysis. Signal intensity (I) was measured on operator-defined regions of interest. The every 4-mm MRIs of
iliac arteries were matched with corresponding histopathological sections of the iliac specimens. All regions of interest foreach sequence were obtained on the same image to avoid variations in signal intensity. Cross-sectional areas of the lumen andthe outer boundary of each iliac section were determined forboth the MRIs and for the histopathological study by manual
tracing with Image-J (10). Cursors for regions of interest
defined by one observer were placed within iliac arteries wall
to measure the T1 and T2 relaxation times. T1 and T2 were
derived from the following respective equations (11):
T1 ¼

T2 ¼

TR
sina,cosb,Ib sinb,cosa,Ialnð
sina,Ib sinb,Ia

TE2  TE1ln ðII12 Þ

Lipid content by percentage (%) was derived from thefollowing respective equations (12):234

Lipid content ð%Þ
IðT 1WIwithoutfatsaturationÞ  IðT 1WIwithfatsaturationÞ
 100¼
IðT 1WIwithoutfatsaturationÞ
Serum Lipid Marker Sampling and Analysis

Blood samples were collected from the peripheral ear arteriesof the rabbits after a 12-hour fast, before starting the cholesterol diet, and at three weeks after injury. Serum total cholesterol (TC) and triglyceride (TG) levels were measured using
the Eiken T-CHO (Eiken Kagaku, Tokyo, Japan) and Triglyceride G test (Wako Chemical, Osaka, Japan) kits, respectively.
Light Microscopy and Immunohistochemistry

The iliac arteries were fixed in 4% paraformaldehyde for24 hours at 4 C, cut into 4-mm intervals, and embedded
in paraffin. Sections (3 mm thick) were morphologicallyevaluated by staining with hematoxylin and eosin/Victoria
blue dye. Serial sections were examined immunohistochemically using the mouse monoclonal primary antismooth muscle actin (HHF35, Dako, Glostrup, Denmark)and anti-macrophage (RAM11, Dako) antibodies. Horseradish peroxidase activity was visualized using 3, 30 -diaminobenzidine tetrahydrochloride, and the sections werefaintly counterstained with Meyer’s hematoxylin.

Academic Radiology, Vol 17, No 2, February 2010

DISCRIMINATION OF UNSTABLE AND STABLE PLAGUE

Figure 4. Magnetic resonance parameters ex vivo and linear regression analyses. (a) T1 and T2 relaxation times, and lipid contents of iliac
arteries in the conventional cholesterol group (CD) (open box) and 0.5% cholesterol (ChD) (dotted box) groups at 3 weeks after balloon injury(n = 8 each; *P < .001). (b) Immunopositive areas for RAM11 and HHF35 of iliac arteries at 3 weeks after balloon injury in both groups (n = 8 each;*P < .001). Data are presented as medians (horizontal bars), quartile ranges (boxes), and 90th percentiles (error bars). (c) Linear regression analysis of associations between relaxation times and immunopositive area in injured iliac arteries.

Immunostaining controls included non-immune mouse
immunoglobulin G instead of the primary antibodies. Areasof positive immunostaining for HHF35 and RAM11 wereanalyzed using a color imaging morphometry system (WinRoof, Mitani, Fukui, Japan). Briefly, immunopositive areas
were extracted using commands to extract colors using
specific protocols based on hue, lightness, and saturation.
Data are expressed as ratios (%) of immunopositive areas
in corresponding areas (13). Two investigators who wereblinded to the treatment assignments morphologicallyanalyzed the specimens.
Statistical Analysis

All data are presented as median and range or interquartile
range or individual dots. Differences for individual groups
were tested using the Mann-Whitney U-test or the Kruskal-Wallis test with Dunn’s multiple comparison test (GraphPad Prizm 4.03, GraphPad Software Inc, San Diego, CA).
The relationships between the factors were evaluated using
Spearman’s rank correlation coefficient. A P value < .05
was considered statistically significant.

542–886 mg/dL vs. 46 mg/dL, 21–56 mg/dL, P < .001; n = 3).
The serum TG level was also significantly higher in the rabbits
fed with ChD than with CD (median; 272 mg/dL, range;
111–375 mg/dL vs. 13 mg/dL, 3–17 mg/dL, P < .001; n = 3).
Magnetic Resonance Angiography 3 Weeks after
Balloon Injury

Magnetic resonance angiograms of the iliac arteries obtained 3
weeks after balloon injury (left femoral artery) revealed
luminal stenosis in both groups of rabbits (Fig 1a-c). Luminal
diameters on conventional and magnetic resonance angiographic images of injured arteries significantly and positively
correlated (Fig 1d).
MRI in vivo 3 Weeks after Balloon Injury

RESULTS

Figure 2 shows the MRIs, T1 and T2 relaxation times, andlipid content of iliac arteries of the rabbits fed with CD andwith ChD. The signal intensity was higher on T1WI, T1
relaxation time was significantly shorter, and lipid content
was higher in the injured arteries of the ChD than of the
CD group. T2 relaxation time did not significantly differ
between the groups.

Serum Concentrations of TC and TG 4 Weeks after
Diets

Histopathological Correlation

The serum concentration of TC was significantly higher in
rabbits fed with ChD than with CD (median; 697 mg/dL, range;

Figure 3 shows the histopathological characteristics of the
injured iliac arteries of the CD and ChD groups. Neointimal
235

KUROIWA ET AL

Academic Radiology, Vol 17, No 2, February 2010

Figure 4. (continued).

formation with luminal stenosis was histologically obvious in
the injured arteries of both groups. The neointima of CDgroup was composed of SMC and extracellular matrix,
whereas that of the ChD group comprised macrophages in
addition to SMC and extracellular matrix (Fig 3a). The areas
immunopositive for RAM11 and for HHF35 in the ChD
group were significantly larger and smaller respectively, thanthose in the CD group (Fig 3b). Replacing primary antibodies
with non-immune mouse IgG did not elicit immunoreactivity (data not shown). The T1 relaxation time in the injured
arteries negatively or positively correlated with areas immunopositive for RAM11 or for HHF35, respectively. The lipid
content in the injured arteries positively or negatively correlated with areas immunopositive for RAM11 or for HHF35,
respectively. The T2 relaxation time in the injured arteries
did not correlate with the immunopositive areas (Fig 3c).
Ex vivo MRI and Histopathological Correlation

Figure 4 shows the T1 and T2 relaxation times and lipid
contents, ex vivo MRIs and histopathological correlationsin injured iliac arteries from both groups. The injured arteriesof the group fed with ChD showed a significantly shorter T1
relaxation time, more lipid contents and macrophages, and less
236

SMCs than those of the group fed with CD (Fig 4a, b). The
T1 relaxation time in the injured arteries negatively or positively correlated with areas immunopositive for RAM11 orfor HHF35, respectively. The lipid content in the injured
arteries positively or negatively correlated with areas immunopositive for RAM11 or for HHF35, respectively. The T2
relaxation time in the injured arteries did not correlate with
the immunopositive areas (Fig 4c). The results were consistent
with those of in vivo study.

DISCUSSION
The present results showed that MRI in vivo can reliably andnoninvasively distinguish macrophage- and lipid-rich atherosclerotic, from SMC-rich rabbit arteries, and that macrophage
contents in the atherosclerotic artery negatively and positively
correlate with T1 relaxation time and lipid content in MRI,
respectively.
The risk of thrombotic complication in atheroscleroticarteries depends on plaque composition rather than luminal
stenosis (14). The likelihood that unstable plaques will cause
thrombotic complications such as myocardial infarction andstroke is high. The histological features of unstable plaquesAcademic Radiology, Vol 17, No 2, February 2010

DISCRIMINATION OF UNSTABLE AND STABLE PLAGUE

include a high lipid content, intensive macrophage accumulation, a large necrotic core with a thin fibrous cap and few
SMCs, whereas abundant SMCs and fibrous connective
tissue characterize stable plaques (15). The degree ofluminal stenosis in the iliac arteries of both groups of
rabbits was similar at 3 weeks after balloon injury in thisstudy. The injured arteries of the ChD group containedlarge numbers of foamy macrophages and fewer SMCs in
the neointima, whereas the neointima of the arteries in
the group fed with CD was composed exclusively of
SMCs with fibrous connective tissue. Although a large
necrotic core did not developed in the lesioned arteriesof the ChD group, these findings are compatible with thoseof human unstable and stable atherosclerotic plaques(14,15). Therefore, this animal model closely simulates
human atherosclerotic vessels.
The T1 relaxation time was significantly shorter and thelipid content was higher in the injured arteries of the ChD,
than the CD group both in vivo and ex vivo. Cappendijk et
al (16) described that semiquantitative analysis of the lipidrich necrotic core of carotid atherosclerotic plaques using
single-sequence T1-weighted turbo field echo MRI is accurate. The composition of lipids in atherosclerotic lesions(cholesterol esters, cholesterol monohydrate, phospholipids,
and triglyceride) changes both chemically and physicallywith the progression of atherosclerosis (17,18). Yuan et al(19) found that triglyceride and hydrated phospholipids havea high contrast-to-noise ratio on T1WI, whereas cholesterol
and cholesterol esters have a low contrast-to-noise ratio atbody temperature. Therefore, triglyceride and hydrated phospholipids among the lipids of the injured arteries of ChD
group might have affected T1 relaxation time, and allowed
quantitation of lipid rich plaque by T1-weighted MRI.
Although several studies have shown that T2-weighted
contrast MRI can help to distinguish between lipid cores,
fibrotic caps, and calcifications (20–22), T2 relaxation time
did not significantly differ between macrophage-rich and
SMC-rich atherosclerotic vessels in the present study. Thismight be due to absence of a large necrotic core with a fibrous
cap and calcification in this model. Nevertheless, our findings
support the notion that MRI can characterize the components
of atherosclerotic plaque and support evaluation of plaquevulnerability (23).
T1 relaxation time or lipid contents in injured arteriescorrelated with areas that were immunopositive for macrophages and SMCs. T1 relaxation time was shorter in macrophage-rich than in SMC-rich atherosclerotic vessels. Helftet al (8,24) reported a significant correlation for plaquecomposition between MRIs and histopathology in ananalysis of lipid and fibrous areas in rabbit aortas. Moreover,the fractional plasma volume and transfer constant ofcontrast material into the extracellular space correlatedwith macrophages and neovasculature (25). Although theresolution has potential limitations for imaging sucha complex histology of atherosclerotic lesions, the present
and previous findings support the notion that MRI canidentify the pathophysiologic characteristics of atherosclerotic plaques. Another limitation of this study is that it is
not known whether this study may translate into larger
animals like humans.
In conclusion, the present findings suggest that T1-relaxation time would be helpful to distinguish macrophage-richfrom SMC-rich plaques. Thus, MRI has considerable potential to assess plaque vulnerability.

REFERENCES
1. Davies MJ. Stability and instability: two faces of coronary atherosclerosis.
Circulation 1996; 94:2013–2020.
2. Morteza N, Libby L, Falk E, et al. From vulnerable plaque to vulnerable
patient. Circulation 2003; 108:1664–1672.
3. Fayad ZA, Fuster V. Characterization of atherosclerotic plaques bymagnetic resonance imaging. Ann NY Acad Sci 2000; 902:173.
4. Saam T, Hatsukami TS, Takaya N, et al. The vulnerable, or high-risk,
atherosclerotic plaque: noninvasive MR imaging for characterization andassessment. Radiology 2007; 244:64–77.
5. Yuan C, Mitsumori LM, Ferguson MS, et al. In vivo accuracy of multispectral magnetic resonance imaging for identifying lipid-rich necrotic coresand intraplaque hemorrhage in advanced human carotid plaques. Circulation 2001; 104:2051–2056.
6. Cai JM, Hatsukami TS, Ferguson MS, et al. Classification of human carotid
atherosclerotic lesions with in vivo multicontrast magnetic resonanceimaging. Circulation 2002; 106:1368–1373.
7. Saam T, Ferguson MS, Yarnykh VJ, et al. Quantitative evaluation of carotid
plaque composition by in vivo MRI. Arterioscler Thromb Vasc Biol 2005;
25:234–239.
8. Helt G, Worthley SG, Fuster V, et al. Atherosclerotic aortic component
quantification by noninvasive magnetic resonance imaging: an in vivo
study in rabbits. J Am Coll Cardiol 2001; 37:1149–1154.
9. Yamashita A, Furukoji E, Marutsuka K, et al. Increased vascular wall
thrombogenicity combined with reduced blood flow promotes occlusive
thrombus formation in rabbit femoral artery. Arterioscler Thromb Vasc
Biol 2004; 24:2420–2424.
10. Rasband, W.S., ImageJ, US National Institutes of Health, Bethesda, MD.
http://rsb.info.nih.gov/ij/, 1997–2008.
11. Ishimori Y, Kimura H, Uematsu H, et al. Dynamic T1 estimation of brain
tumors using double-echo dynamic MR imaging. J Magn Reson Imaging
2003; 18:113–120.
12. Griffin JF, Yeung D, Antonio GE, et al. Vertebral marrow fat content anddiffusion and perfusion indexes in woman with varying bone density: MR
evaluation. Radiology 2006; 241:831–838.
13. Yamashita A, Shoji K, Tsuruda T, et al. Medial and adventitial macrophages are associated with expansive atherosclerotic remodeling in rabbit
femoral artery. Histol Histopathol 2008; 23:127–136.
14. Fayad ZA, Fuster V. Clinical imaging of the high-risk or vulnerable atherosclerotic plaque. Circ Res 2001; 89:305–316.
15. Fuster V, Moreno PR, Fayad ZA, et al. Atherothrombosis and high-risk plaque. J Am Coll Cardiol 2005; 46:937–954.
16. Cappendijk VC, Heeneman S, Kessels A, et al. Comparison of singlesequence T1w TFE MRI with multisequence MRI for the quantification oflipid-rich necrotic core in atherosclerotic plaque. J Magn Reson Imaging
2008; 27:1347–1355.
17. Katz SS, Shipley GG, Small DM. Physical chemistry of the lipids ofhuman atherosclerotic lesions. Demonstration of a lesion intermediate
between fatty streaks and advanced plaques. J Clin Invest 1976; 58:
200–211.
18. Small DM, Shipley GG. Physical-chemical basis of lipid deposition inatherosclerosis. Science 1974; 185:222–229.
19. Yuan C, Petty C, O’Brien KD, et al. In vitro and in situ magnetic resonanceimaging signal features of atherosclerotic plaque-associated lipids. Arterioscler Thromb Vasc Biol 1997; 17:1496–1503.
20. Yuan C, Tsuruda JS, Beach KN, et al. Techniques for high-resolution
MR imaging of atherosclerotic plaque. J Magn Reson Imaging 1994; 4:43–49.
21. Toussaint JF, Southern JF, Fuster V, et al. T2 contrast for NMR characterization of human atherosclerosis. Arterioscler Thromb Vasc Biol 1995; 15:1533–1542.

237

KUROIWA ET AL

22. Serfaty JM, Chaabane L, Tabib A, et al. Atherosclerotic plaques: classification and characterization with T2-weighted high-spatial-resolution MR
imaging-an in vitro study. Radiology 2001; 219:403–410.
23. Saam T, Hatsukami TS, Takaya N, et al. The vulnerable, or high-risk,
atherosclerotic plaque: noninvasive MR imaging for characterization andassessment. Radiology 2007; 244:64–77.

238

Academic Radiology, Vol 17, No 2, February 2010

24. Helft G, Worthley SG, Fuster V, et al. Progression and regression of atherosclerotic lesions: monitoring with serial noninvasive magnetic resonanceimaging. Circulation 2002; 105:993–998.
25. Kerwin WS, O’brien KD, Ferguson MS, et al. Inflammation in carotid
atherosclerotic plaque: a dynamic contrast-enhanced MR imaging study.
Radiology 2006; 241:459–468.